Working conditions in women with multiple pregnancy-the impact on preterm birth and adherence to guidelines: a prospective cohort study.

BACKGROUND: Women with multiple pregnancies are at risk for maternal complications such as preterm birth. Hazardous working conditions, such as physically demanding work and long and irregular working hours, might increase the risk of preterm birth. OBJECTIVE: This study primarily aimed to determine whether certain working conditions up to 20 weeks of pregnancy increase the risk of preterm birth in multiple pregnancies. The secondary objective was to evaluate whether the working conditions of Dutch women with multiple pregnancy have been adjusted to the guidelines of the Netherlands Society of Occupational Medicine. STUDY DESIGN: We performed a prospective cohort study alongside the ProTWIN trial, a multicenter randomized controlled trial that assessed whether cervical pessaries could effectively prevent preterm birth. Women with paid work of >8 hours per week completed questionnaires concerning general health and working conditions between 16 and 20 weeks of pregnancy. Univariable and multivariable logistic regression analyses were performed to identify work-related factors associated with preterm birth (32-36 weeks' gestation) and very preterm birth (<32 weeks' gestation). We analyzed a subgroup of participants who worked for more than half of the week (>28 hours). We calculated the proportion of women who reported work-related factors not in accordance with guidelines. RESULTS: We studied 383 women, of whom 168 (44%) had been randomized to pessary, 142 (37%) to care as usual, and 73 (19%) did not participate in the randomized part of the study. After adjusting for confounding variables, working >28 hours was associated with very preterm birth (n=33; 78%) (adjusted odds ratio, 3.0; 95% confidence interval, 1.1-8.1), and irregular working times were associated with preterm birth (n=26, 17%) (adjusted odds ratio, 2.0; 95% confidence interval, 1.0-4.1) and very preterm birth (n=10; 24%) (adjusted odds ratio, 2.7; 95% confidence interval, 1.0-7.3). Within a subgroup of 213 participants working >28 hours per week, multivariable analysis showed that irregular working times (n=16; 20%) (adjusted odds ratio, 3.5; 95% confidence interval, 1.2-10.1) and no/little freedom in performance of tasks (n=23; 28%) (adjusted odds ratio, 3.0; 95% confidence interval, 1.3-7.3) were associated with preterm birth. Irregular working times (n=9; 27%) (adjusted odds ratio, 3.4; 95% confidence interval, 1.0-11.1), requiring physical strength (n=9; 27%) (adjusted odds ratio, 5.3; 95% confidence interval, 1.6-17.8), high physical workload (n=7; 21%) (adjusted odds ratio, 3.9; 95% confidence interval, 1.1-13.9), and no/little freedom in performing tasks (n=10; 30%) (adjusted odds ratio, 3.2; 95% confidence interval, 1.1-9.6) were associated with very preterm birth. Before 20 weeks of pregnancy, 224 (58.5%) women with multiple pregnancy continued to work under circumstances that were not in accordance with the guidelines. CONCLUSION: In our cohort study, nearly 60% of women with multiple pregnancy continued to work under circumstances not in accordance with the guidelines to avoid physical and job strain and long and irregular working hours. Irregular hours were associated with preterm and very preterm birth, and long hours were associated with preterm birth.

More home births during the COVID-19 pandemic in the Netherlands.

BACKGROUND: The aim of this observational study was to examine whether the course of pregnancy and birth and accompanying outcomes among low-risk pregnant women changed in the COVID-19 pandemic compared to the prepandemic period. METHODS: We analyzed data from the Dutch Midwifery Case Registration System (VeCaS). Differences in the course of pregnancy and birth, and accompanying maternal and neonatal outcomes, were calculated between women pregnant during the initial months of the COVID-19 pandemic (March 1 to August 3, 2020) and the prepandemic period (March 1-August 3, 2019). We also conducted a stratified analysis by parity. RESULTS: We included 5913 low-risk pregnant women of whom 2963 (50.1%) were pregnant during the first surge of the COVID-19 pandemic, and 2950 (49.9%) in the prepandemic period. During the COVID-19 pandemic, more women desired and had a home birth. More women used pain medication and fewer had an episiotomy in the COVID-19 period than prior. Multiparous women had a higher suspected rate of fetal growth restriction during COVID; however, the actual rate of small for gestational age infants was not significantly increased. We observed no differences for onset and augmentation of labor or for mode of birth, though the rate of vaginal births increased. CONCLUSIONS: During the COVID-19 pandemic, there was a higher rate of planned and actual home birth, and suspected growth restriction and a lower rate of episiotomy among low-risk pregnant women in the Netherlands.

Working conditions in low risk nulliparous women in The Netherlands: are legislation and guidelines a guarantee for a healthy working environment? A cohort study.

OBJECTIVE: Hazardous working conditions increase the risk of adverse pregnancy outcomes. In this study, we examine adherence to legislation and guidelines aimed at improving working conditions in pregnancy. METHODS: Between 2014 and 2016, we recruited a prospective cohort of low-risk nulliparous pregnant women in paid employment or self-employed in 16 community midwifery practices in The Netherlands. Participants completed two questionnaires concerning demographics, education, general health and working conditions between 10-16 and 20-24 weeks of pregnancy. We calculated the proportion of participants with work-related risk factors not in accordance with legislation and/or guidelines. RESULTS: Of 269 participants included, 214 (80%) completed both questionnaires. At 10-16 weeks 110 (41%) participants and at 20-24 weeks 129 (63%) participants continued to work under circumstances that did not meet recommendations. Employers provided mandated information on work adjustment to 37 (15%) participants and 96 (38%) participants received no information about the potential hazards while working with biological and chemical hazards. Participants with lower educational attainment (aOR 2.2 95%CI 1.3-3.9), or employment in healthcare (aOR 4.5, 95%CI 2.2-9.0), education/childcare and social service (aOR 2.6, 95%CI 1.1-6.0 2),, catering (aOR 3.6, 95%CI 1.1-12) and industry, construction and cleaning (aOR 3.3, 95%CI 1.1-10.3) more often continued work which did not meet recommendations. CONCLUSION: There is poor adherence to national legislation and guidelines for safe working in pregnancy in The Netherlands: 50% of the pregnant women worked under hazardous conditions. Given the impact on adverse pregnancy outcomes as well as on the public purse, action to improve compliance must be taken by all stakeholders.

Evaluation of a blended care programme for caregivers and working pregnant women to prevent adverse pregnancy outcomes: an intervention study.

OBJECTIVE: Work-related activities can be a risk factor for pregnancy complications such as preterm birth. This study evaluates the effectiveness of a blended care programme, Pregnancy and Work, that provides pregnant workers and their obstetrical caregivers with advice on work adjustment. METHODS: Women less than 20 weeks of gestation, in paid employment or self-employed, in the care of four participating hospitals and their referring midwifery practices in the Netherlands received either the blended care programme (n=119), consisting of a training for professionals and a mobile health application, or care as usual (n=122) in a controlled intervention study with a follow-up in intervention and control populations. All participants completed three questionnaires concerning health and working conditions at 16, 24 and 32 weeks of pregnancy. Primary outcome was the percentage of women who received advice from their obstetrical caregiver about work adjustment. Secondary outcomes were work status, realised work adjustment and working conditions. Groups were compared using univariate and multivariate regression analyses. RESULTS: A total of 188 (78%) completed all three questionnaires. In the blended care group, women received more advice from obstetrical caregivers to adjust their work than in the control group, 41 (39%) vs 21 (18%) (adjusted relative risk (aRR) 2.2, 95% CI 1.4 to 3.4), but less from their employer 8 (8%) vs 31 (28%) (aRR 0.29, 95% CI 0.14 to 0.61). There were no significant differences in realised work adjustments. At 24 weeks, 30% of the pregnant women in both groups continued to work in hazardous workplaces. CONCLUSION: Among working pregnant women, the blended care intervention increases advice on work adjustment given by midwives and obstetricians, but does not lead to more work adjustments.

Continuous glucose monitoring during diabetic pregnancy (GlucoMOMS): A multicentre randomized controlled trial.

AIM: Diabetes is associated with a high risk of adverse pregnancy outcomes. Optimal glycaemic control is fundamental and is traditionally monitored with self-measured glucose profiles and periodic HbA1c measurements. We investigated the effectiveness of additional use of retrospective continuous glucose monitoring (CGM) in diabetic pregnancies. MATERIAL AND METHODS: We performed a nationwide multicentre, open label, randomized, controlled trial to study pregnant women with type 1 or type 2 diabetes who were undergoing insulin therapy at gestational age < 16 weeks, or women who were undergoing insulin treatment for gestational diabetes at gestational age < 30 weeks. Women were randomly allocated (1:1) to intermittent use of retrospective CGM or to standard treatment. Glycaemic control was assessed by CGM for 5-7 days every 6 weeks in the CGM group, while self-monitoring of blood glucose and HbA1c measurements were applied in both groups. Primary outcome was macrosomia, defined as birth weight above the 90th percentile. Secondary outcomes were glycaemic control and maternal and neonatal complications. RESULTS: Between July 2011 and September 2015, we randomized 300 pregnant women with type 1 (n = 109), type 2 (n = 82) or with gestational (n = 109) diabetes to either CGM (n = 147) or standard treatment (n = 153). The incidence of macrosomia was 31.0% in the CGM group and 28.4% in the standard treatment group (relative risk [RR], 1.06; 95% CI, 0.83-1.37). HbA1c levels were similar between treatment groups. CONCLUSIONS: In diabetic pregnancy, use of intermittent retrospective CGM did not reduce the risk of macrosomia. CGM provides detailed information concerning glycaemic fluctuations but, as a treatment strategy, does not translate into improved pregnancy outcome.

Nifedipine versus atosiban for threatened preterm birth (APOSTEL III): a multicentre, randomised controlled trial.

BACKGROUND: In women with threatened preterm birth, delay of delivery by 48 h allows antenatal corticosteroids to improve neonatal outcomes. For this reason, tocolytics are often administered for 48 h; however, there is no consensus about which drug results in the best maternal and neonatal outcomes. In the APOSTEL III trial we aimed to compare the effectiveness and safety of the calcium-channel blocker nifedipine and the oxytocin inhibitor atosiban in women with threatened preterm birth. METHODS: We did this multicentre, randomised controlled trial in ten tertiary and nine teaching hospitals in the Netherlands and Belgium. Women with threatened preterm birth (gestational age 25-34 weeks) were randomly assigned (1:1) to either oral nifedipine or intravenous atosiban for 48 h. An independent data manager used a web-based computerised programme to randomly assign women in permuted block sizes of four, with groups stratified by centre. Clinicians, outcome assessors, and women were not masked to treatment group. The primary outcome was a composite of adverse perinatal outcomes, which included perinatal mortality, bronchopulmonary dysplasia, sepsis, intraventricular haemorrhage, periventricular leukomalacia, and necrotising enterocolitis. Analysis was done in all women and babies with follow-up data. The study is registered at the Dutch Clinical Trial Registry, number NTR2947. FINDINGS: Between July 6, 2011, and July 7, 2014, we randomly assigned 254 women to nifedipine and 256 to atosiban. Primary outcome data were available for 248 women and 297 babies in the nifedipine group and 255 women and 294 babies in the atosiban group. The primary outcome occurred in 42 babies (14%) in the nifedipine group and in 45 (15%) in the atosiban group (relative risk [RR] 0·91, 95% CI 0·61-1·37). 16 (5%) babies died in the nifedipine group and seven (2%) died in the atosiban group (RR 2·20, 95% CI 0·91-5·33); all deaths were deemed unlikely to be related to the study drug. Maternal adverse events did not differ between groups. INTERPRETATION: In women with threatened preterm birth, 48 h of tocolysis with nifedipine or atosiban results in similar perinatal outcomes. Future clinical research should focus on large placebo-controlled trials, powered for perinatal outcomes. FUNDING: ZonMw (the Netherlands Organisation for Health Research and Development).

Low dose aspirin in the prevention of recurrent spontaneous preterm labour - the APRIL study: a multicenter randomized placebo controlled trial.

BACKGROUND: Preterm birth (birth before 37 weeks of gestation) is a major problem in obstetrics and affects an estimated 15 million pregnancies worldwide annually. A history of previous preterm birth is the strongest risk factor for preterm birth, and recurrent spontaneous preterm birth affects more than 2.5 million pregnancies each year. A recent meta-analysis showed possible benefits of the use of low dose aspirin in the prevention of recurrent spontaneous preterm birth. We will assess the (cost-)effectiveness of low dose aspirin in comparison with placebo in the prevention of recurrent spontaneous preterm birth in a randomized clinical trial. METHODS/DESIGN: Women with a singleton pregnancy and a history of spontaneous preterm birth in a singleton pregnancy (22-37 weeks of gestation) will be asked to participate in a multicenter, randomized, double blinded, placebo controlled trial. Women will be randomized to low dose aspirin (80 mg once daily) or placebo, initiated from 8 to 16 weeks up to maximal 36 weeks of gestation. The primary outcome measure will be preterm birth, defined as birth at a gestational age (GA) < 37 weeks. Secondary outcomes will be a composite of adverse neonatal outcome and maternal outcomes, including subgroups of prematurity, as well as intrauterine growth restriction (IUGR) and costs from a healthcare perspective. Preterm birth will be analyzed as a group, as well as separately for spontaneous or indicated onset. Analysis will be performed by intention to treat. In total, 406 pregnant women have to be randomized to show a reduction of 35% in preterm birth from 36 to 23%. If aspirin is effective in preventing preterm birth, we expect that there will be cost savings, because of the low costs of aspirin. To evaluate this, a cost-effectiveness analysis will be performed comparing preventive treatment with aspirin with placebo. DISCUSSION: This trial will provide evidence as to whether or not low dose aspirin is (cost-) effective in reducing recurrence of spontaneous preterm birth. TRIAL REGISTRATION: Clinical trial registration number of the Dutch Trial Register: NTR 5675 . EudraCT-registration number: 2015-003220-31.

Which Factors Contribute to False-Positive, False-Negative, and Invalid Results in Fetal Fibronectin Testing in Women with Symptoms of Preterm Labor?

Objective We assessed the influence of external factors on false-positive, false-negative, and invalid fibronectin results in the prediction of spontaneous delivery within 7 days. Methods We studied symptomatic women between 24 and 34 weeks' gestational age. We performed uni- and multivariable logistic regression to estimate the effect of external factors (vaginal soap, digital examination, transvaginal sonography, sexual intercourse, vaginal bleeding) on the risk of false-positive, false-negative, and invalid results, using spontaneous delivery within 7 days as the outcome. Results Out of 708 women, 237 (33%) had a false-positive result; none of the factors showed a significant association. Vaginal bleeding increased the proportion of positive fetal fibronectin (fFN) results, but was significantly associated with a lower risk of false-positive test results (odds ratio [OR], 0.22; 95% confidence intervals [CI], 0.12-0.39). Ten women (1%) had a false-negative result. None of the investigated factors was significantly associated with a significantly higher risk of false-negative results. Twenty-one tests (3%) were invalid; only vaginal bleeding showed a significant association (OR, 4.5; 95% CI, 1.7-12). Conclusion The effect of external factors on the performance of qualitative fFN testing is limited, with vaginal bleeding as the only factor that reduces its validity.

The predictive value of quantitative fibronectin testing in combination with cervical length measurement in symptomatic women.

BACKGROUND: The combination of the qualitative fetal fibronectin test and cervical length measurement has a high negative predictive value for preterm birth within 7 days; however, positive prediction is poor. A new bedside quantitative fetal fibronectin test showed potential additional value over the conventional qualitative test, but there is limited evidence on the combination with cervical length measurement. OBJECTIVE: The purpose of this study was to compare quantitative fetal fibronectin and qualitative fetal fibronectin testing in the prediction of spontaneous preterm birth within 7 days in symptomatic women who undergo cervical length measurement. STUDY DESIGN: We performed a European multicenter cohort study in 10 perinatal centers in 5 countries. Women between 24 and 34 weeks of gestation with signs of active labor and intact membranes underwent quantitative fibronectin testing and cervical length measurement. We assessed the risk of preterm birth within 7 days in predefined strata based on fibronectin concentration and cervical length. RESULTS: Of 455 women who were included in the study, 48 women (11%) delivered within 7 days. A combination of cervical length and qualitative fibronectin resulted in the identification of 246 women who were at low risk: 164 women with a cervix between 15 and 30 mm and a negative fibronectin test (<50 ng/mL; preterm birth rate, 2%) and 82 women with a cervix at >30 mm (preterm birth rate, 2%). Use of quantitative fibronectin alone resulted in a predicted risk of preterm birth within 7 days that ranged from 2% in the group with the lowest fibronectin level (<10 ng/mL) to 38% in the group with the highest fibronectin level (>500 ng/mL), with similar accuracy as that of the combination of cervical length and qualitative fibronectin. Combining cervical length and quantitative fibronectin resulted in the identification of an additional 19 women at low risk (preterm birth rate, 5%), using a threshold of 10 ng/mL in women with a cervix at <15 mm, and 6 women at high risk (preterm birth rate, 33%) using a threshold of >500 ng/mL in women with a cervix at >30 mm. CONCLUSION: In women with threatened preterm birth, quantitative fibronectin testing alone performs equal to the combination of cervical length and qualitative fibronectin. Possibly, the combination of quantitative fibronectin testing and cervical length increases this predictive capacity. Cost-effectiveness analysis and the availability of these tests in a local setting should determine the final choice.

Effectiveness of a cervical pessary for women who did not deliver 48 h after threatened preterm labor (Assessment of perinatal outcome after specific treatment in early labor: Apostel VI trial).

BACKGROUND: Preterm birth is a major cause of neonatal mortality and morbidity. As preventive strategies are largely ineffective, threatened preterm labor is a frequent problem that affects approximately 10 % of pregnancies. In recent years, risk assessment in these women has incorporated cervical length measurement and fetal fibronectin testing, and this has improved the capacity to identify women at increased risk for delivery within 14 days. Despite these improvements, risk for preterm birth continues to be increased in women who did not deliver after an episode of threatened preterm labor, as indicated by a preterm birth rate between 30 to 60 % in this group of women. Currently no effective treatment is available. Studies on maintenance tocolysis and progesterone have shown ambiguous results. The pessary has not been evaluated in women with threatened preterm labor, however studies in asymptomatic women with a short cervix show reduced rates of preterm birth rates as well as perinatal complications. The APOSTEL VI trial aims to assess the effectiveness of a cervical pessary in women who did not deliver within 48 h after an episode of threatened preterm labor. METHODS/DESIGN: This is a nationwide multicenter open-label randomized clinical trial. Women with a singleton or twin gestation with intact membranes, who were admitted for threatened preterm labor, at a gestational age between 24 and 34 weeks, a cervical length between 15 and 30 mm and a positive fibronectin test or a cervical length below 15 mm, who did not deliver after 48 h will be eligible for inclusion. Women will be allocated to a pessary or no intervention (usual care). Primary outcome is preterm delivery < 37 weeks. Secondary outcomes are amongst others a composite of perinatal morbidity and mortality. Sample size is based on an expected 50 % reduction of preterm birth before 37 weeks (two-sided test, α 0.05 and ß 0.2). Two hundred women with a singleton pregnancy need to be randomized. Analysis will be done by intention to treat. DISCUSSION: The APOSTEL VI trial will provide evidence whether a pessary is effective in preventing preterm birth in women who did not deliver 48 h after admission for threatened preterm labor and who remain at high risk for preterm birth. TRIAL REGISTRATION: Trial is registered at the Dutch Trial Register: http://www.trialregister.nl , NTR4210, date of registration: October 16th 2013.

Impact of fetal gender on the risk of preterm birth, a national cohort study.

INTRODUCTION: Fetal gender is associated with preterm birth; however, a proper subdivision by onset of labor and corresponding neonatal outcome by week of gestation is lacking. MATERIAL AND METHODS: Data from the Netherlands Perinatal Registry (1999-2010) were used to calculate relative risk ratios for gender by week of gestation and gender-related risk on adverse neonatal outcomes using a moving average technique. White European women with an alive fetus at onset of labor were included. Adverse neonatal outcomes were defined as neonatal mortality and a composite of neonatal morbidity. Onset of labor was categorized as spontaneous onset with intact membranes, premature rupture of membranes, and induction or elective cesarean section. RESULTS: The study population comprised 1 736 615 singleton deliveries (25(+0) -42(+6) weeks). Male fetuses were at increased risk of spontaneous preterm birth with intact membranes compared with a female fetus with a peak between 27 and 31 weeks [relative risk (RR) 1.5; 95% CI 1.4-1.6]. Male fetuses were also at increased risk of preterm premature rupture of membranes between 27 and 37 weeks (RR 1.2; 95% CI 1.16-1.23). No gender effect was seen for medically indicated preterm birth. No significant differences were seen for neonatal mortality. Males were at significantly increased risk of composite neonatal morbidity from 29 weeks onwards (RR 1.3; 95% CI 1.3-1.4). CONCLUSIONS: Male fetal gender is a relevant risk factor for spontaneous preterm birth, both for intact membranes and for preterm premature rupture of membranes in white European women. In addition, male infants are at increased risk of neonatal morbidity.

Early nasogastric tube feeding in optimising treatment for hyperemesis gravidarum: the MOTHER randomised controlled trial (Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding).

BACKGROUND: Hyperemesis gravidarum (HG), or intractable vomiting during pregnancy, is the single most frequent cause of hospital admission in early pregnancy. HG has a major impact on maternal quality of life and has repeatedly been associated with poor pregnancy outcome such as low birth weight. Currently, women with HG are admitted to hospital for intravenous fluid replacement, without receiving specific nutritional attention. Nasogastric tube feeding is sometimes used as last resort treatment. At present no randomised trials on dietary or rehydration interventions have been performed. Small observational studies indicate that enteral tube feeding may have the ability to effectively treat dehydration and malnutrition and alleviate nausea and vomiting symptoms. We aim to evaluate the effectiveness of early enteral tube feeding in addition to standard care on nausea and vomiting symptoms and pregnancy outcomes in HG patients. METHODS/DESIGN: The MOTHER trial is a multicentre open label randomised controlled trial ( www.studies-obsgyn.nl/mother ). Women ≥ 18 years hospitalised for HG between 5 + 0 and 19 + 6 weeks gestation are eligible for participation. After informed consent participants are randomly allocated to standard care with intravenous rehydration or early enteral tube feeding in addition to standard care. All women keep a weekly diary to record symptoms and dietary intake until 20 weeks gestation. The primary outcome will be neonatal birth weight. Secondary outcomes will be the 24-h Pregnancy Unique Quantification of Emesis and nausea score (PUQE-24), maternal weight gain, dietary intake, duration of hospital stay, number of readmissions, quality of life and side-effects. Also gestational age at birth, placental weight, umbilical cord plasma lipid concentration and neonatal morbidity will be evaluated. Analysis will be according to the intention to treat principle. DISCUSSION: With this trial we aim to clarify whether early enteral tube feeding is more effective in treating HG than intravenous rehydration alone and improves pregnancy outcome. TRIAL REGISTRATION NUMBER: NTR4197 . Date of registration: October 2(nd) 2013.

Implementation of client versus care-provider strategies to improve external cephalic version rates: a cluster randomized controlled trial.

OBJECTIVE: To determine the effectiveness of a client or care-provider strategy to improve the implementation of external cephalic version. DESIGN: Cluster randomized controlled trial. SETTING: Twenty-five clusters; hospitals and their referring midwifery practices randomly selected in the Netherlands. POPULATION: Singleton breech presentation from 32 weeks of gestation onwards. METHODS: We randomized clusters to a client strategy (written information leaflets and decision aid), a care-provider strategy (1-day counseling course focused on knowledge and counseling skills), a combined client and care-provider strategy and care-as-usual strategy. We performed an intention-to-treat analysis. MAIN OUTCOME MEASURES: Rate of external cephalic version in various strategies. Secondary outcomes were the percentage of women counseled and opting for a version attempt. RESULTS: The overall implementation rate of external cephalic version was 72% (1169 of 1613 eligible clients) with a range between clusters of 8-95%. Neither the client strategy (OR 0.8, 95% CI 0.4-1.5) nor the care-provider strategy (OR 1.2, 95% CI 0.6-2.3) showed significant improvements. Results were comparable when we limited the analysis to those women who were actually offered intervention (OR 0.6, 95% CI 0.3-1.4 and OR 2.0, 95% CI 0.7-4.5). CONCLUSIONS: Neither a client nor a care-provider strategy improved the external cephalic version implementation rate for breech presentation, neither with regard to the number of version attempts offered nor the number of women accepting the procedure.

Risk stratification with cervical length and fetal fibronectin in women with threatened preterm labor before 34 weeks and not delivering within 7 days.

OBJECTIVE: To stratify the risk of spontaneous preterm delivery using cervical length (CL) and fetal fibronectin (fFN) in women with threatened preterm labor who remained pregnant after 7 days. DESIGN: Prospective observational study. SETTING: Nationwide cohort of women with threatened preterm labor from the Netherlands. POPULATION: Women with threatened preterm labor between 24 and 34 weeks with a valid CL and fFN measurement and remaining pregnant 7 days after admission. METHODS: Kaplan-Meier and Cox proportional hazards models were used to estimate cumulative percentages and hazard ratios (HR) for spontaneous delivery. MAIN OUTCOME MEASURES: Spontaneous delivery between 7 and 14 days after initial presentation and spontaneous preterm delivery before 34 weeks. RESULTS: The risk of delivery between 7 and 14 days was significantly increased for women with a CL < 15 mm or a CL ≥15 to <30 mm and a positive fFN, compared with women with a CL ≥30 mm: HR 22.3 [95% confidence interval (CI) 2.6-191] and 14 (95% CI 1.8-118), respectively. For spontaneous preterm delivery before 34 weeks the risk was increased for women with a CL < 15 mm [HR 6.3 (95% CI 2.6-15)] or with a CL ≥15 to <30 mm with either positive fFN [HR 3.6 (95% CI 1.5-8.7)] or negative fFN [HR 3.0 (95% CI 1.2-7.1)] compared with women with a CL ≥ 30 mm. CONCLUSIONS: In women remaining pregnant 7 days after threatened preterm labor, CL and fFN results can be used in risk stratification for spontaneous delivery.

Term breech deliveries in the Netherlands: did the increased cesarean rate affect neonatal outcome? A population-based cohort study.

OBJECTIVE: The aim of this study was to evaluate the effect of the increased cesarean rate for term breech presentation on neonatal outcome. We also investigated whether the clinical case selection for vaginal delivery applied by Dutch obstetricians led to an optimization of neonatal outcome, or whether there is still room for improvement in terms of perinatal outcome. DESIGN: Retrospective cohort. SETTING: The Netherlands. POPULATION: Singleton term breech deliveries from 37+0 to 41+6 weeks, excluding fetuses with congenital malformations or antenatal death. METHOD: We used data from the Dutch national perinatal registry from 1999 up to 2007. MAIN OUTCOME MEASURES: Perinatal mortality and morbidity. RESULTS: We studied 58,320 women with a term breech delivery. There was an increase in the elective cesarean rate (from 24 to 60%). As a consequence, overall perinatal mortality decreased [1.3 0/00 vs. 0.7 0/00;odds ratio 0.51 (95% confidence interval 0.28­0.93)], whereas it remained stable in the planned vaginal birth group [1.7 0/00 vs. 1.6 0/00; odds ratio 0.96(95% confidence interval 0.52­1.76)]. The number of cesareans done to prevent one perinatal death was 338. CONCLUSIONS: Adjustment of the national guidelines after publication of the Term Breech Trial resulted in a shift towards elective cesarean and a decrease of perinatal mortality and morbidity among women delivering a child in breech at term. Still, 40% of these women attempt vaginal birth. The relative safety of an elective cesarean should be weighed against the consequences of a scarred uterus in future pregnancies.

Nifedipine versus atosiban in the treatment of threatened preterm labour (Assessment of Perinatal Outcome after Specific Tocolysis in Early Labour: APOSTEL III-Trial).

BACKGROUND: Preterm birth is the most common cause of neonatal morbidity and mortality. Postponing delivery for 48 hours with tocolytics to allow for maternal steroid administration and antenatal transportation to a centre with neonatal intensive care unit facilities is the standard treatment for women with threatening preterm delivery in most centres. However, there is controversy as to which tocolytic agent is the drug of first choice. Previous trials have focused on tocolytic efficacy and side effects, and are probably underpowered to detect clinically meaningfull differences in neonatal outcome. Thus, the current evidence is inconclusive to support a balanced recommendation for clinical practice. This multicenter randomised clinical trial aims to compare nifedipine and atosiban in terms of neonatal outcome, duration of pregnancy and maternal side effects. METHODS/DESIGN: The Apostel III trial is a nationwide multicenter randomised controlled study. Women with threatened preterm labour (gestational age 25 - 34 weeks) defined as at least 3 contractions per 30 minutes, and 1) a cervical length of ≤ 10 mm or 2) a cervical length of 11-30 mm and a positive Fibronectin test or 3) ruptured membranes will be randomly allocated to treatment with nifedipine or atosiban. Primary outcome is a composite measure of severe neonatal morbidity and mortality. Secondary outcomes will be time to delivery, gestational age at delivery, days on ventilation support, neonatal intensive care (NICU) admittance, length admission in neonatal intensive care, total days in hospital until 3 months corrected age, convulsions, apnoea, asphyxia, proven meningitis, pneumothorax, maternal side effects and costs. Furthermore, an economic evaluation of the treatment will be performed. Analysis will be by intention to treat principle. The power calculation is based on an expected 10% difference in the prevalence of adverse neonatal outcome. This implies that 500 women have to be randomised (two sided test, ß 0.2 at alpha 0.05). DISCUSSION: This trial will provide evidence on the optimal drug of choice in acute tocolysis in threatening preterm labour. CLINICAL TRIAL REGISTRATION: NTR2947, date of registration: June 20th 2011.

Implementation of external cephalic version in the Netherlands: a retrospective cohort study.

BACKGROUND: External cephalic version (ECV) reduces the rate of elective cesarean sections as a result of breech presentation. Several studies have shown that not all eligible women undergo an ECV attempt. The aim of this study was to evaluate the implementation of ECV in the Netherlands and to explain variation in implementation rates with hospital characteristics and individual factors. METHODS: We invited 40 hospitals to participate in this retrospective cohort study. We reviewed hospital charts for all singleton breech deliveries from 36 weeks' gestation and onwards between January 2008 and December 2009. We documented whether an ECV attempt was performed, reasons for not performing an attempt, mode of delivery, and hospital characteristics. RESULTS: We included 4,770 women from 36 hospitals. ECV was performed in 2,443 women (62.2% of eligible women, range 8.2-83.6% in different hospitals). Implementation rates were higher in teaching hospitals, hospitals with special office hours for ECV, larger obstetric units, and hospitals located in larger cities. Suboptimal implementation was mainly caused by health care providers who did not offer ECV. CONCLUSION: ECV implementation rates vary widely among hospitals. Suboptimal implementation is mostly caused by the care provider not offering the treatment and secondly due to women not opting for the offered attempt. A prerequisite for designing a proper implementation strategy is a detailed understanding of the exact reasons for not offering and not opting for ECV.

Contraindications for external cephalic version in breech position at term: a systematic review.

OBJECTIVE: External cephalic version (ECV) is a safe and effective intervention that can prevent breech delivery, thus reducing the need for cesarean delivery. It is recommended in national guidelines. These guidelines also mention contraindications for ECV, and thereby restrict the application of ECV. We assessed whether the formulation of these contraindications in guidelines are based on empiric data. DESIGN: Systematic review. POPULATION: Pregnant women with a singleton breech presentation from 34 weeks. METHODS: We searched the National Guideline Clearinghouse, the Cochrane Central Register of Controlled Trials, MEDLINE (1953-2009), EMBASE (1980-2009), TRIP database (until 2011), NHS (National Health Services, until 2011), Diseases database (until 2011) and NICE guidelines (until 2011) for existing guidelines on ECV and studied the reproducibility of the contraindications stated in the guidelines. Furthermore, we systematically reviewed the literature for contraindications and evidence on these contraindications. MAIN OUTCOME MEASURES: Contraindications of ECV. RESULTS: We found five guidelines mentioning 18 contraindications, varying from five to 13 per guideline. The contraindications were not reproducible between the guidelines with oligohydramnios as the only contraindication mentioned in all guidelines. The literature search yielded 60 studies reporting on 39 different contraindications, of which we could only assess evidence of six of them. CONCLUSION: The present study shows that there is no general consensus on the eligibility of patients for ECV. Therefore we propose to limit contraindications for ECV to clear empirical evidence or to those with a clear pathophysiological relevance.

Stress-reducing interventions in pregnancy for the prevention of preterm birth: a systematic review and meta-analysis.

Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality. Maternal stress during pregnancy is an established risk factor for PTB. We aimed to review the effects of stress-reducing interventions during pregnancy on PTB. Studies reporting on stress-reducing interventions during pregnancy and PTB rates in general low-risk obstetric populations were included. PTB rates, low birth weight (LBW) rates, mean gestational age and birth weight, maternal anxiety and stress, and adverse perinatal outcomes were investigated. Data were extracted using a standardized extraction form, pooled effect sizes were calculated with the random effects model. Ten studies with a total of 4.816 women were included. The interventions included Pilates, yoga, a multidisciplinary stress reduction program, combination therapy (combining mindfulness, yoga, music, baby bonding, and education), and hypnosis. The incidence of PTB was significantly lower in the intervention group (RR 0.50, 95% CI 0.35 - 0.71). The overall quality of the included studies was low, and the risk of bias was high. In conclusion, this study provides evidence supporting the potential efficacy of stress-reducing interventions in reducing the incidence of PTB in low-risk women. We propose a RCT of high quality to determine the effectiveness of stress-reducing interventions in reducing PTB risk.

External validation of a prediction model for successful external cephalic version.

We sought external validation of a prediction model for the probability of a successful external cephalic version (ECV). We evaluated the performance of the prediction model with calibration and discrimination. For clinical practice, we developed a score chart to calculate the probability of a successful ECV. We studied 320 women undergoing ECV, of which 117 (37%) were successful. The model underestimated the success rate by 4 to 14%. The area under the receiver operating characteristic curve was moderate (0.66; 95% confidence interval: 0.60 to 0.72), but the model was able to make good distinction between women with a higher predicted probability of a successful ECV (more than 50%) compared with women with a lower predicted probability of a successful ECV (less than 20%). Our model to predict the outcome of ECV holds in external validation. It can be used to support patient counseling and decision making for ECV in singleton term breech presentations.